Neuroprotection in Acute Ischemic Stroke
מילות מפתח
תַקצִיר
תיאור
This will be a pilot trial exploring the ability of a novel combination ("H2M") of molecular hydrogen (an antioxidant) and minocycline (a widely used antibiotic known to inhibit the activation of matrix metallo-proteinase-9 and poly(ADP-ribose) polymerase), to protect brain tissue from ischemia/reperfusion injury that occurs during and after an ischemic stroke. Both hydrogen and minocycline have excellent safety profiles, have been previously demonstrated individually to reduce infarction in animal models of stroke, and have potentially synergistic mechanisms of action against ischemic brain damage. The mechanisms of action of both agents would be specifically relevant to patients receiving tissue plasminogen activator (tPA) or thrombectomy, and achieving some degree of therapeutic reperfusion.
This will be a double blinded, placebo-controlled trial. Eligible and willing subjects will be randomly assigned to be treated with either H2M or placebo, in addition to standard treatments. The treatment with H2M or placebo will start as soon as possible after diagnosis of stroke, and continue for three days (hydrogen) and five days (minocycline) respectively. Measures of stroke severity and disability will be recorded at baseline, and through a follow-up phone call (45 days) and clinic visit (90 days).
תאריכים
| אומת לאחרונה: | 01/31/2019 |
| הוגש לראשונה: | 10/19/2017 |
| ההרשמה המשוערת הוגשה: | 10/19/2017 |
| פורסם לראשונה: | 10/23/2017 |
| העדכון האחרון הוגש: | 02/21/2019 |
| עדכון אחרון פורסם: | 02/25/2019 |
| תאריך תחילת לימוד בפועל: | 08/01/2017 |
| תאריך סיום משוער משוער: | 08/01/2020 |
| תאריך סיום משוער ללימודים: | 11/01/2020 |
מצב או מחלה
התערבות / טיפול
Drug: Hydrogen/Minocycliine
Drug: Hydrogen/Minocycliine
Other: Placebo Hydrogen/Placebo Minocycline
Other: Placebo Hydrogen/Placebo Minocycline
שלב
קבוצות זרועות
| זְרוֹעַ | התערבות / טיפול |
|---|---|
| Experimental: Hydrogen/Minocycliine Hydrogen will be infused into aqueous solution (normal saline or water) at as high a concentration as possible (saturation = 1.6 ppm), and administered intravenously or orally respectively, q 8 hours for 3 days.
Similarly, Minocycline will be administered either i.v. or p.o. once daily for 5 days. | Drug: Hydrogen/Minocycliine Hydrogen will be infused into bags of normal saline solution and administered intravenously, or infused into water for the patient to drink, as the patient's condition permits. This will be administered q 8 hours for 3 days. |
| Placebo Comparator: Placebo Hydrogen/Placebo Minocycline Normal saline will be substituted for both Hydrogen and Minocycline for intravenous administration. Water will be substituted for hydrogen when administered p.o., and placebo capsules will be substituted for minocycline. | Other: Placebo Hydrogen/Placebo Minocycline Normal saline solution or water will be administered i.v. or p.o. respectively, in place of hydrogen solution. |
קריטריונים לזכאות
| גילאים הזכאים ללימודים | 18 Years ל 18 Years |
| מינים הזכאים ללימודים | All |
| מקבל מתנדבים בריאים | כן |
| קריטריונים | Inclusion Criteria: 1. Aged 18 years old or over 2. Presenting to/at SBUH with acute ischemic stroke 3. Baseline (at admission to study) National Institute of Health Stroke Scale (NIHSS) between 5-22 inclusive 4. Administration of study medication possible within 24 hours of last known well - Exclusion Criteria: 1. Other major diseases of the central nervous system, including brain tumors, Alzheimer's disease, Parkinson's disease, demyelinating disease, inflammatory brain or vascular disease, craniotomy, traumatic encephalopathy, or idiopathic intracranial hypertension* 2. Pre-existing neurological disability (historical NIHSS > 0); unable to live independently 3. Severe stroke or comorbidities likely to result in patient dying within 3 months 4. Acute or chronic renal failure with calculated creatinine clearance < 30 5. Liver disease leading to > 2x elevation in liver transaminases or significant loss of synthetic capacity* 6. Thrombocytopenia (<100x109platelets / L blood) 7. Pre-existing infectious disease requiring antibiotic therapy 8. Pregnancy or nursing. Females of reproductive age will be required to use barrier contraception or abstain from sexual intercourse while on study medications, as minocycline may render oral contraceptives less effective. 9. Known allergy to tetracycline group of drugs 10. Concurrent treatment with retinoids or ergot alkaloids 11. Inability to safely tolerate the fluid load (iv NS or po water) associated with study medication* 12. Treatment with another investigational drug within the last 30 days that may interfere with this study's medications* 13. Inability to tolerate or comply with study procedures* |
תוֹצָאָה
מדדי תוצאות ראשוניים
1. simplified modified Rankin Scale (sMRSq) [90 days]
אמצעי תוצאה משניים
1. simplified modified Rankin Scale (sMRSq) [45 days]
2. NIH Stroke Scale (NIHSS) [90 days]
